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RESEARCH PRODUCT

Genome Wide Association Scan identifies new variants associated with a cognitive predictor of dyslexia

Heikki LyytinenFranck RamusDénes TóthJacqueline HulslanderRichard K. OlsonFabien FauchereauBertram Müller-myhsokKarin LanderlBruce F. PenningtonJohn C. DefriesJoel B. TalcottAlessandro GialluisiDaniel BrandeisJohn F. SteinErik G. WillcuttUrs MaurerBeate St PourcainSilvia ParacchiniClyde FrancksGerd Schulte-körneShelley D. SmithGuillaume HuguetMyriam Peyrard-janvidTill F. M. AndlauerNazanin Mirza-schreiberAndrew P. MorrisAnthony P. MonacoPaavo H.t. LeppänenThomas BourgeronJuha KereSimon E. FisherAnniek VaessenWilliam M. BrandlerKristina MollKerstin U. LudwigJohannes SchumacherMarkus M. NöthenThomas S. ScerriPer HoffmannMilene BonteValéria CsépeFerenc HonbolygóDarina Czamara

subject

0303 health sciencesmedia_common.quotation_subjectDyslexiaShort-term memoryGenomicsGenome-wide association studyCognitionmedicine.diseaseSpelling03 medical and health sciences0302 clinical medicineReading (process)medicineCognitive skillPsychology030217 neurology & neurosurgery030304 developmental biologyClinical psychologymedia_common

description

AbstractDevelopmental dyslexia (DD) is one of the most prevalent learning disorders among children and is characterized by deficits in different cognitive skills, including reading, spelling, short term memory and others. To help unravel the genetic basis of these skills, we conducted a Genome Wide Association Study (GWAS), including nine cohorts of reading-impaired and typically developing children of European ancestry, recruited across different countries (N=2,562-3,468).We observed a genome-wide significant effect (p<1×10−8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2 withinMIR924HG (micro-RNA 924 host gene;p= 4.73×10−9), and a suggestive association on 8q12.3 withinNKAIN3(encoding a cation transporter;p= 2.25 ×10−8). RAN represents one of the best universal predictors of reading fluency across orthographies and linkage to RAN has been previously reported withinCELF4(18q12.2), a gene highly expressed in the fetal brain which is co-expressed withNKAIN3and predicted to be a target ofMIR924. These findings suggest new candidate DD susceptibility genes and provide insights into the genetics and neurobiology of dyslexia.

10.1101/309336http://dx.doi.org/10.1101/309336